Effects of verapamil and ryanodine on activity of the embryonic chick heart during anoxia and reoxygenation.
Perturbations of the trans-sarcolemmal and sarcoplasmic Ca2+ transport contribute to the abnormal myocardial activity provoked by anoxia and reoxygenation. Whether Ca2+ pools of the extracellular compartment and sarcoplasmic reticulum (SR) are involved to the same extent in the dysfunction of the anoxic-reoxygenated immature heart has not been investigated. Spontaneously contracting hearts isolated from 4-day-old chick embryos were submitted to repeated anoxia (1 min) followed by reoxygenation (5 min). Heart rate, atrioventricular propagation velocity, ventricular shortening, velocities of contraction and relaxation, and incidence of arrhythmias were studied, recorded continuously. Addition of verapamil (10 nM), which blocks selectively sarcolemmal L-type Ca2+ channels, was expected to protect against excessive entry of extracellular Ca2+, whereas addition of ryanodine (10 nM), which opens the SR Ca2+ release channel, was expected to increase cytosolic Ca2+ concentration. Verapamil (a) had no dromotropic effect by contrast to adult heart, (b) attenuated ventricular contracture induced by repeated anoxia, (c) shortened cardioplegia induced by reoxygenation, and (d) had remarkable antiarrhythmic properties during reoxygenation specially. On the other hand, ryanodine potentiated markedly arrhythmias both during anoxia and at reoxygenation. Thus despite its immaturity, the SR seems to be functional early in the developing chick heart and involved in the reversible dysfunction induced by anoxia-reoxygenation. Moreover, Ca2+ entry through L-type channels appears to worsen arrhythmias especially during reoxygenation. These findings show that the Ca2+-handling systems involved in irregular activity in immature heart, such as the embryonic chick heart, may differ from those in the adult.
Tenthorey
D
D
Institute of Physiology, Faculty of Medicine, University of Lausanne, Switzerland.
de Ribaupierre
Y
Y
Kucera
P
P
Raddatz
E
E
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002642:Chick Embryo; D003286:Contracture; D006321:Heart / Q000187:drug effects* / Q000196:embryology / Q000503:physiopathology; D006323:Heart Arrest; D006339:Heart Rate / Q000187:drug effects; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D010100:Oxygen / Q000097:blood / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D012433:Ryanodine; D014700:Verapamil; D010100:Oxygen